title: Gamma-glutamylcysteine synthetase deficiency and hemolytic anemia.
abstract: gamma-Glutamylcysteine synthetase is one of the enzymes of glutathione (GSH) synthesis. A deficiency of this enzyme has been found only once previously in humans: it was associated with spinocerebellar degeneration and hemolytic anemia. We report the case of a woman, daughter of fifth cousins, who was gamma-glutamylcysteine-synthetase-deficient. Modest decreases in the amount of GSH in cultured lymphoblasts and fibroblasts could be documented. The amount of residual enzyme was insufficient to permit detailed studies of the characteristics of the mutant enzymes, but no major abnormality in its Km for cysteine and glutamic acid or in its heat stability were found. In contrast to the earlier report, the only manifestation of the enzyme deficiency was hemolytic anemia. This leads us to conclude that either the occurrence of neurologic symptoms in the other reported family was a chance association or that the clinical expression of this rare defect is pleomorphic.
authors.affiliation: Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, La Jolla, CA 92037.
authors.forename: E
authors.initials: E
authors.lastname: Beutler
authors.forename: R
authors.initials: R
authors.lastname: Moroose
authors.forename: L
authors.initials: L
authors.lastname: Kramer
authors.forename: T
authors.initials: T
authors.lastname: Gelbart
authors.forename: L
authors.initials: L
authors.lastname: Forman
mesh_terms: D000328:Adult; D000743:Anemia, Hemolytic / Q000201:enzymology*; D005260:Female; D005978:Glutathione / Q000172:deficiency*; D005981:Glutathione Synthase / Q000172:deficiency*; D006801:Humans; D010375:Pedigree; D010453:Peptide Synthases / Q000172:deficiency*
chemical_list: D010453:Peptide Synthases; D005981:Glutathione Synthase; D005978:Glutathione